Effect and underlying mechanism of L-carnitine improving myocardial systolic dysfunction in sepsis mice

WANG Zhihua; ZHOU Yuanqun; XIANG Xinming; ZHANG Qianwei; OUYANG Xingnan; ZHANG Jie; LI Tao; TIAN Linqiang; LIU Liangming

doi:10.16016/j.2097-0927.202507037

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Effect and underlying mechanism of L-carnitine improving myocardial systolic dysfunction in sepsis mice

Basic Medicine | 更新时间：2025-11-13

- Effect and underlying mechanism of L-carnitine improving myocardial systolic dysfunction in sepsis mice
- Journal of Army Medical University Vol. 47, Issue 21, Pages: 2630-2640(2025)
- 作者机构：
  
  1.新乡医学院第三附属医院外科，河南新乡
  2.陆军军医大学大坪医院战伤休克与输血研究室，创伤与化学中毒全国重点实验室，重庆
- 作者简介：
  
  TIAN Linqiang，E-mail：wstiansenzhi@126.com
  LIU Liangming，E-mail：lmliu62@tmmu.edu.cn
- 基金信息：
  
  the Key Program of the National Natural Science Foundation of China(82430082);the Youth Program of the National Natural Science Foundation of China(82402549)
- DOI：10.16016/j.2097-0927.202507037
  CLC： R322.11;R631.2;R977.4
- Received：09 July 2025，
  
  Revised：2025-10-17，
  
  Accepted：23 October 2025，
  
  Published：15 November 2025
- 稿件说明：
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王志华，周远群，向鑫明，等.左旋肉碱对脓毒症心肌收缩功能障碍的改善作用及机制［J］.陆军军医大学学报，2025，47（21）：2630-2640.DOI：10.16016/j.2097-0927.202507037.

WANG Z H， ZHOU Y Q， XIANG X M，et al.Effect and underlying mechanism of L-carnitine improving myocardial systolic dysfunction in sepsis mice［J］.J Army Med Univ，2025，47（21）：2630-2640.DOI：10.16016/j.2097-0927.202507037.
王志华，周远群，向鑫明，等.左旋肉碱对脓毒症心肌收缩功能障碍的改善作用及机制［J］.陆军军医大学学报，2025，47（21）：2630-2640.DOI：10.16016/j.2097-0927.202507037. DOI：

WANG Z H， ZHOU Y Q， XIANG X M，et al.Effect and underlying mechanism of L-carnitine improving myocardial systolic dysfunction in sepsis mice［J］.J Army Med Univ，2025，47（21）：2630-2640.DOI：10.16016/j.2097-0927.202507037. DOI：

摘要

目的

探讨左旋肉碱（L-carnitine）对脓毒症心肌收缩功能障碍的改善作用及其机制。

方法

采用盲肠结扎穿孔术（cecal ligation and puncture，CLP）建立小鼠脓毒症模型，将10周龄SPF级雄性C57BL/6小鼠（体质量20~30 g）按照随机数字表法分为5组：假手术（Sham）组，脓毒症（Sepsis）组，左旋肉碱（L-carnitine）组，左旋肉碱治疗+依托莫司［L-carnitine+Etomoxir（Eto）］组，Eto组。利用超声心动图检测小鼠心功能，ELISA方法检测血清中肌酸激酶同工酶MB（creatine kinase-MB isoenzyme， CK-MB）水平，记录小鼠72 h存活情况，以评估L-carnitine对心脏功能的影响。分离心肌细胞，利用细胞微张力仪检测心肌细胞收缩功能与钙瞬变。取各组小鼠心肌组织，采用ELISA方法检测甘油三酯（triglyceride

，

TG）、游离脂肪酸（free fatty acid

，

FFA）和三磷酸腺苷（adenosine triphosphate， ATP）含量。采用脂多糖（lipopolysaccharide

，

LPS）刺激HL-1心肌细胞12 h，构建脓毒症体外模型，分为正常（CTRL）组、LPS组、左旋肉碱（L-carnitine）组、左旋肉碱治疗+依托莫司（L-carnitine+Eto）组和依托莫司（Eto）组。采用ELISA检测心肌细胞中TG、FFA和ATP含量以及肉碱棕榈酰转移酶1A（carnitine palmitoyltransferase 1A

，

CPT1A）的活性，利用细胞能量代谢分析系统检测脂肪酸氧化能力，采用Western blot检测心肌细胞CPT1A的蛋白表达；采用BODIPY-FL-C16（绿色荧光标记的棕榈酸）孵育细胞，利用激光共聚焦显微镜观察棕榈酸在细胞质和线粒体的分布。

结果

与Sham组比较，Sepsis组小鼠心功能明显受损，表现为射血分数、平均动脉血压降低（

0.05），且心损标志物CK-MB水平升高（

0.05），L-carnitine处理显著改善脓毒症小鼠心肌功能并恢复血压，使脓毒症小鼠的存活率从12.50%提升至81.25%

（P<

0.05）。与Sham组比较，Sepsis组急性分离的单个心肌细胞的收缩功能和钙瞬变显著下降（

0.05），L-carnitine治疗可显著恢复脓毒症心肌细胞的收缩功能和钙释放能力（

0.05）。体内外实验均发现，Sepsis组和LPS组TG和FFA含量升高（

0.05），ATP含量降低（

0.05），L-carnitine处理可显著逆转此现象。LPS组心肌细胞对脂肪酸的基础氧化速率、最大氧化能力较CTRL组显著降低（

0.05），L-carnitine治疗可明显改善上述指标。与CTRL组比较，LPS组心肌细胞中CPT1A的表达和活性明显降低（

0.05），L-carnitine处理明显增加CPT1A的表达和活性（

0.05）。LPS组心肌细胞中绿色荧光标记的棕榈酸主要在细胞质形成大量颗粒或团块状聚集，且与线粒体共定位极少，L-carnitine组心肌细胞胞质的绿色荧光颗粒较小，且与线粒体共定位增加，而L-carnitine+Eto组与LPS组呈相似的现象。此外，体内外实验均发现，CPT1A抑制剂Eto处理逆转了L-carnitine的作用，L-carnitine+Eto组中ATP的含量较L-carnitine组显著降低（

0.05），而FFA含量显著增加（

0.05）。

结论

左旋肉碱通过CPT1A依赖性机制促进脂肪酸进入线粒体进行β-氧化，从而改善脓毒症心肌细胞脂肪酸氧化功能障碍，进一步改善脓毒症心肌细胞收缩功能。

Abstract

Objective

To explore the protective effect of L-carnitine on myocardial systolic dysfunction in sepsis and its underlying mechanism.

Methods

A mouse sepsis model was established by cecal ligation and puncture (CLP). Ten-week-old male SPF-grade C57BL/6 mice (body weight 20~30 g) were randomly divided into 5 groups

via

random number table: Sham group

Sepsis group

L-carnitine group

L-carnitine+Etomoxir (Eto) group

and Eto group. Echocardiography assessed cardiac function

ELISA measured serum creatine kinase isoenzyme MB (CK-MB) levels

and 72-hour survival rates were recorded to evaluate L-carnitine’s effects on cardiac function. Cardiomyocytes were isolated

and a cell microtensiometer was used to detect cardiomyocyte contractile function and calcium transients. Myocardial tissues were collected from each group

and ELISA was used to determine the contents of triglyceride (TG)

free fatty acid (FFA)

and adenosine triphosphate (ATP).An

in vitro

sepsis model was constructed by stimulating HL-1 cardiomyocytes with lipopolysaccharide (LPS) for 12 hours

which was divided into 5 groups: control (CTRL) group

LPS group

L-carnitine group

L-carnitine + Eto group

and Eto group. ELISA was used to dete

ct the contents of TG

FFA

and ATP as well as the activity of carnitine palmitoyltransferase 1A (CPT1A) in cardiomyocytes. A cellular energy metabolism analysis system was employed to measure fatty acid oxidation capacity

and Western blot was used to detect the protein expression of CPT1A in cardiomyocytes. BODIPY-FL-C16 (green fluorescently labeled palmitic acid) was utilized to detect the distribution of fatty acids in the cytoplasm and mitochondria

via

immunofluorescence technology

thereby observing the ability of cells to transport fatty acids into mitochondria.

Results

Compared with the Sham group

cardiac function was significantly impaired in the Sepsis group

as evidenced by decreased ejection fraction and mean arterial pressure (

0.05)

along with elevated levels of the cardiac injury marker CK-MB (

0.05). Treatment with L-carnitine significantly improved myocardial function

restored blood pressure in septic mice

and increased their survival rate from 12.50% to 81.25% (

0.05).Compared with the Sham group

the contractile function and calcium transients of acutely isolated single cardiomyocytes were significantly reduced in the Sepsis group (

0.05)

while L-carnitine treatment remarkably restored the contractile function and calcium release capacity of septic cardiomyocytes (

0.05).Both

in vivo

and

in vitro

experiments showed that TG and FFA levels were significantly increased (

0.05)

and ATP levels was significantly decreased (

0.05) in the Sepsis and LPS groups—effects significantly reversed by L-carnitine treatment. Compared with the CTRL group

the basal oxidation rate and maximum oxidation capacity of fatty acids in cardiomyocytes of the LPS group were significantly reduced (

0.05)

and L-carnitine treatment notably improved these indicators.Compare

d with the CTRL group

the expression and activity of CPT1A in cardiomyocytes of the LPS group were significantly decreased (

0.05)

while L-carnitine treatment significantly increased the expression and activity of CPT1A (

0.05). In LPS group cardiomyocytes

green fluorescently labeled palmitic acid primarily formed numerous granular/clumpy aggregates in the cytoplasm with minimal mitochondrial colocalization. In the L-carnitine group

the green fluorescent granules in the cytoplasm of cardiomyocytes were smaller

and colocalization with mitochondria was increased. However

the L-carnitine + Eto group exhibited similar phenomena to the LPS group.In addition

both

in vivo

and

in vitro

experiments demonstrated that treatment with the CPT1A inhibitor Eto reversed the effect of L-carnitine. Compared with the L-carnitine group

the ATP content in the L-carnitine + Eto group was significantly decreased (

0.05)

while the FFA content was significantly increased (

0.05).

Conclusion

L-carnitine facilitates fatty acid entry into mitochondria for β-oxidation

via

a CPT1A-dependent mechanism

thereby ameliorating fatty acid oxidation dysfunction in septic cardiomyocytes and improving myocardial contractile function.

关键词

Keywords

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